This invention relates to a fermentation process for producing certain carboxylic acids. More particularly, the invention concerns a method of improving the rate of production of certain carboxylic acids in Rhizopus cultures by use of selected growth media additives.
Production of certain carboxylic acids, e.g., fumaric acid, by fungi of the genus Rhizopus has been a subject of several patents and other contributions to the technical literature. Rhodes et al., Appl. Microbiol. 7:74-80 (1959), describe a series of fermentation experiments in which optimal conditions were sought for maximizing fumaric acid yields in Rhizopus arrhizus cultures. In a later publication, Appl. Microbiol. 10:9-15 (1962), Rhodes et al. describe preferred conditions for producing fumaric acid by fermentation of Rhizopus arrhizus in 20 liter fermentors. In particular, use of a polypropylene glycol to control foaming, and CaCO.sub.3 to continuously neutralize the resulting fumaric acid, are disclosed.
Waksman, U.S. Pat. No. 2,326,986, describe a method for producing fumaric acid by fermentation of Rhizopus nigricans, or other fungi of the order Mucorales, in the presence of zinc and iron salts. Kane, et al., U.S. Pat. No. 2,327,191, disclose a process for producing fumaric acid by submerged aerobic fermentation of Rhizopus nigricans. Lubowitz, et al., U.S. Pat. No. 2,861,922, disclose use of nickel salts to promote fumaric acid production by Rhizopus fungi. La Roe, U.S. Pat. No. 2,912,363, describes improvements in fumaric acid yields by Rhizopus and related fungi which are attributable to limiting the concentration of nitrogen sources in culture media.
A number of patents or publications disclose that fats, fatty acids, or their derivatives can be added to microbial fermentation media as supplemental carbon sources, or as yield promoters in fermentation processes for producing glutamic acid and certain antibiotics. For example, U.K. Pat. Nos. 679,087 and 700,316 disclose use of fats or fatty acids as carbon sources or supplements.
A series of papers by Takinami et al., Agr. Biol. Chem. 27:858-863 (1963); 28:114-119 (1964); and 29:351-359 (1965); disclose methods of promoting L-glutamic acid yields in Brevibacterium lactofermentum fermentations by addition of fatty acid esters and other fatty acid derivatives, e.g., polyoxyethylene sorbitan monostearate. Trumpy, et al., J. Gen. Microbiol. 30:381-393 (1963) and Millis, et al., J. Gen. Microbiol. 30:365-379 (1963) report improved yields of citric acid in cultures of Aspergillus niger to which oils with a high content of unsaturated fatty acids, e.g., peanut oil, were added.
Fermentation processes, especially those employing inexpensive and abundant carbon sources derived from biomass, offer alternative sources of supply of commercially important organic acids. Such organic acids include fumaric acid, which is utilized by the plastics industry in the manufacture of polyester and alkyd resins; lactic and malic acids, which are utilized by the food industry; and succinic acid, which is consumed in the manufacture of pharmaceuticals, plastics, and protective coatings. Thus, improved fermentation processes for producing these compounds are desirable.